Combination of Amino Acid/Dipeptide with Nitric Oxide Donating Oleanolic Acid Derivatives as PepT1 Targeting Antitumor Prodrugs

By taking advantage of the cytotoxic effect of nitric oxide (NO) and PepT1 for molecule-targeted drug delivery, a series of amino acid/dipeptide diester prodrugs of NO-donating oleanolic acid derivatives were designed and synthesized. Two prodrugs 6a and 8a showed potent cytotoxcity, which is probably due to their high PepT1 affinity and NO-releasing ability. Furthermore, the aqueous solubility of the prodrugs was also significantly enhanced because of the hydrophilic amino acid/dipeptide promoiety.